Centrocytic lymphoma is a biologically distinct subtype of B-cell lymphoma that has been associated with chromosome 11 bcl-1 rearrangements and PRAD1 overexpression. Objectives of the proposal are: 1) to study the bcl-1 rearrangement and translocation junction in centrocytic lymphoma in order to determine the chromosomal locations, translocation sites and nucleotide sequences of the translocation junction; this will include bracketing and isolating the translocation junction from a number of centrocytic lymphomas with bcl-1 rearrangement using libraries of tumor genomic DNA. Subclones from across the breakpoint will be used for chromosomal mapping and in situ hybridization and the nucleotide sequence of the breakpoint adjacent to the bcl-1 region will be determined, and 2) to further dissect the bcl-1/PRAD1 genomic region and identify translocation-related breakpoints in cases of centrocytic lymphoma that show PRAD1 overexpression but not bcl-1 rearrangements; this will entail bi-directional chromosome walking with restriction enzyme mapping and nucleotide sequence analysis to physically link the bcl-1 region and PRAD1 region, and thus develop new DNA probes that can detect translocation breakpoints in this region.
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